Solubilizer and external preparations containing the same

ABSTRACT

Percutaneously absorbable preparations which comprise, by weight, 0.001 to 20%, preferably 0.1 to 20%, of 3-l-menthoxy-propane-1,2-diol as a solubilizer for a drug and 0.001 to 20%, preferably 0.5 to 10%, of the drug as two essential ingredients, the balance being other ingredients as adjuvants selected from water-soluble polymers, monohydric alcohols, polyhydric alcohols, rosin esters, water, fatty acid esters, hydrocarbons, softening agents, emulsifying agents. The preparations are in the forms of poultice, plasters, ointments, gels, creams, gel-like creams, lotions, reserver patches, liniments, aerosols and may be used in packs.

TECHNICAL FIELD

The present invention relates to a solubilizing agent or solubilizer fora pharmaceutically effective ingredient and an external preparationcontaining the solubilizer. In particular, the present invention relatesto a solubilizer for an efficacious ingredient used in a percutaneouslyabsorbable preparation such as poultice or for a fat-soluble powder usedin a pack, the solubilizer being excellent in solubilization of such aneffective ingredient as well as in safety, stability, compatibility,non-odorousness and refreshing, effect, and also relates to an externalpreparation containing the solubilizer.

BACKGROUND ART

Up to this time, many attempts have been made to attain desirablecurative effects by the percutaneous absorption of drugs. It is asignificant problem in such percutaneously absorbable preparations howefficiently the drug (active ingredient as a drug) is released from thebase, i.e., how efficiently the drug migrates from the base to the skin.In general, when attempting to design a preparation using some drugtherein, there frequently occurs a case that the drug crystallizes inthe base because of its insufficient dissolution therein, resulting inpoor drug release so that a sufficient curative effect is not achieved.Accordingly, the selection of an optimum solubilizer for a drug is animportant factor in designing such a preparation. If an unsuitablesolubilizer is selected for a drug, the release of the drug from thebase is lowered due to the insufficient dissolution of the drug in thebase, which leads to poor migration of the drug to an affected part sothat poor curative effect results.

Solubilizers currently used for drugs include alcohols, glycols, severalsurfactants, essential oils such as peppermint oil, crotamiton, methylsalicylate, glycol salicylate and fatty acid esters such as isopropylmyristate.

For example, Japanese Pat. Appln. Laid-Open Gazette No. 154413/1981discloses an anti-inflammatory agent for external use which comprisesboth an oil-in-water emulsion containing a solution of flurbiprofen in aterpene or in a fatty acid ester and an aqueous base, and Japanese Pat.Appln. Laid-Open Gazette No. 98209/1982 discloses anotheranti-inflammatory agent for external use which is prepared by dissolvingindomethacin in a mono- or polyhydric alcohol or the like.

However, these solubilizers have problems because they have poorsolubilizability (capability of solubilization) to cause thecrystallization of a drug, they are limited in use due to their odors,they bleed from the base with the lapse of time due to their poorcompatibility with the base, they are poor in stability to causedecomposition or discoloration with the lapse of time and they causeundesirable side effects due to their stimuli to the skin, resulting inunsatisfactory effects in many cases.

Meanwhile, attempts have been made to get a powder which is soluble infat or difficultly soluble in water (hereinafter referred to as"fat-soluble powder") to be contained in a pack for its practical use.However, a pack generally comprises a water-soluble base which exhibitsextremely poor solubilizability for a fat-soluble powder, so that manyof the above attempts were accompanied by the problems that thesolubilization of the powder in the base was difficult and/or that theresulting pack was poor in stability to cause crystallization of thepowder with the lapse of time even when the powder could be solubilizedin the base in the preparation stage.

SUMMARY OF THE INVENTION

The present invention aims at solving the above problems to provide asolubilizer which exhibits excellent solubilizability for apharmaceutically effective ingredient and is excellent in safety,stability and compatibility, and provides an external preparationcontaining the solubilizer.

The above object of the present invention can be attained by using3-l-menthoxypropane-1,2-diol as the solubilizer for a pharmaceuticallyeffective ingredient.

Namely, the present invention resides in a solubilizer for apharmaceutically effective ingredient which is composed of3-l-menthoxypropane-1,2-diol, and in an external preparation containingthe solubilizer and a pharmaceutically effective ingredient.

The term "pharmaceutically effective ingredient" used in thisspecification refers to a drug used in a percutaneously absorbablepreparation or a fat-soluble powder used in a pack.

3-l-menthoxypropane-1,2-diol which is the solubilizer of the presentinvention, is a known substance described in, e.g., Japanese Pat. Appln.Laid-Open Gazette No. 88334/1983 as a substance having a cooling orrefreshing activity. Further, Japanese Pat. Appln. Laid-Open Gazette No.25908/1985 discloses that this compound is useful as a cosmeticmaterial, has an excellent cooling effect and is extremely safe for theskin. However, there has not been made even any attempt to solubilize apharmaceutically effective ingredient such as a drug by using said knownsubstance, to say nothing of an attempt to get a drug solubilized by useof this substance to be absorbed percutaneously. In other words, such anattempt has been made for the first time by the inventors of the presentinvention and the present invention is based on this entirely newfinding.

According to the present invention, the amount of3-l-menthoxypropane-1,2-diol contained in an external preparation is0.001 to 20% by weight of the total amount of the external preparation.

In particular, when the external preparation is a percutaneouslyabsorbable preparation containing a drug as the effective ingredient and3-l-menthoxypropane-1,2-diol is used as a solubilizer, the amount of3-l-menthoxypropane-1,2-diol used will be 0.1 to 20% by weight,preferably 0.5 to 10% by weight, of the total amount of the externalpreparation. When the amount is less than 0.1% by weight, no sufficienteffects as the solubilizer will be exhibited, while when it exceeds 20%by weight, no stable preparation will be prepared.

The drug to be used in the percutaneously absorbable preparation whichis one of the external preparations according to the present inventionis not particularly limited but may be any one selected from among knownconventional drugs. Such drugs include steroidal anti-inflammatoryagents such as prednisolone, dexamethasone, hydrocortisone, fluocinoloneacetonide, betamethasone valerate, betamethasone dipropionate,clobetasone butyrate and prednisolone succinate; nonsteroidalanti-inflammatory agents such as indomethacin, diclofenac, ibuprofen,ketoprofen, flufenamic acid, ketorolac, flurbiprofen, felbinac,suprofen, pranoprofen, tiaprofen, loxoprofen and tenidap, and theirester derivatives; antiallergic agents such as tranilast, azelastine,ketotifen, ibudilast and emedastine; antihistamic agents such asdiphenhydramine, chlorpheniramine, promethazine and tripelennamihe;central nervous system stimulants such as chlorpromazine, nitrazepam,diazepam, phenobarbital and reserpine; hormones such as insulin,testosterone, norethisterone, methyltestosterone, progesterone andestradiol; antihypertensive agents such as clonidine, reserpine andguanethidine sulfate; cardiotonics such as digitoxin and digoxin;antiarrhythmic agents such as propranolol hydrochloride, procainamidehydrochloride, ajimalin, pindolol and tulobuterol hydrochloride;coronary vasodilators such as nitroglycerin, isosorbide dinitrate,papaverine hydrochloride and nifedipine; local anesthetics such aslidocaine, benzocaine, procaine hydrochloride and tetracaine; analgeticagents such as morphine, aspirin, codeine, acetanilide and aminopyrine;skeletal muscle relaxants such as eperisone, tizanidine, tolperisone andinaperisone; antifungal agents such as acetophenylamine, nitrofurazone,pentamycin, naphthiomate, miconazole, omoconazole, clotrimazole,butenafine hydrochloride and bifonazole; antineoplastic agents such as5-fluorouracil, busulfan, actinomycin, bleomycin and mitomycin;antidysurics such as terodiline hydrochloride and oxybutyninhydrochloride; antiepileptics such as nitrazepam and meprobamate;antiparkinson agents such as chlorzoxazone and levodopa; assistant tothe prohibition of smoking such as nicotine; vitamins and prostaglandin,though the drug usable in the percutaneously absorbable preparation isof course not limited to them.

The amount of the drug used is preferably 0.001 to 20% by weight, morepreferably 0.5 to 10% by weight, of the total amount of the externalpreparation, though it is not particularly limited.

The dosage form of the percutaneously absorbable preparation of thepresent invention is not particularly limited, but may be any oneselected from among conventional poultice, plaster, ointment, gel,cream, gel-type cream, lotion, reserver-type patch, liniment, aerosoland so forth.

The poultice and plaster according to the present invention will now bedescribed below.

In preparing the poultice, a hydrophilic base comprising a water-solublepolymer, a polyhydric alcohol and water is used in consideration oflong-term stability, releasability, percutaneous absorbability andsafety for the skin.

The water-soluble polymer to be used in the hydrophilic base may be oneor more members suitably selected from the group consisting of gelatin,casein, pullulan, dextran, sodium alginate, soluble starch,carboxystarch, dextrin, carboxymethylcellulose, sodiumcarboxymethylcellulose, methylcellulose, ethylcellulose,hydroxyethylcellulose, polyvinyl alcohol, polyethylene oxide,polyacrylic acid, polyacrylamide, polysodium acrylate,polyvinylpyrrolidone, carboxyvinyl polymer, polyvinyl ether,methoxyethylene-maleic anhydride copolymer, isobutylenemaleic anhydridecopolymer, N-vinylacetamide, copolymer comprising N-vinylacetamide andacrylic acid and/or acrylate salt and so forth. The amount of thewater-soluble polymer used is 1 to 30% by weight, preferably 1 to 20% byweight, more preferably 1 to 15% by weight, based on the total amount ofthe preparation. When the amount is less than 1% by weight, theresulting preparation will have too low a viscosity to retain its shape,while when it exceeds 30% by weight, the resulting mixture of theconstituents will have a high viscosity to lower the workability inpreparing a homogeneous dispersion of the constituents or in applyingthe dispersion.

The polyhydric alcohol is one or more members suitably selected from thegroup consisting of polyethylene glycol, propylene glycol, dipropyleneglycol, polypropylene glycol, 1,3-butylene glycol, 1,4-butylene glycol,isobutylene glycol, glycerol, diglycerol, sorbitol and so forth. Theamount of the polyhydric alcohol used is 10 to 90% by weight, preferably10 to 70% by weight, more preferably 20 to 60% by weight. When theamount is less than 10% by weight, the resulting preparation willexhibit poor humectant effect, while when it exceeds 90% by weight, thesolubility of the water-soluble polymer will be adversely affected. Theamount of water used is 10 to 90% by weight, preferably 20 to 80% byweight. The water serves to solubilize the water-soluble polymer tothereby make the polymer develop its thickening, cohesive andshape-retaining properties.

If necessary, the base of the poultice may further contain one or morecrosslinking agents in addition to the above essential components. Thecrossliking agents include polyvalent metal compounds such as aluminumhydroxide, aluminum chloride, calcium hydroxide, calcium chloride,aluminum sulfate, aluminum ammonium sulfate, aluminum potassium sulfate,magnesium aluminometasilicate and dihydroxyaluminum aminoacetate; andcompounds each having at least two epoxy groups in the molecule such asethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether,propylene glycol diglycidyl ether, polypropylene glycol diglycidylether, polytetramethylene glycol diglycidyl ether, glycerol polyglycidylether, polyglycerol polyglycidyl ether, sorbitol polyglycidyl ether,sorbitan polyglycidyl ether, trimethylolpropane polyglycidyl ether,pentaerythritol polyglycidyl ether, resorcinol diglycidyl ether,neopentyl glycol diglycidyl ether and 1,6-hexanediol diglycidyl ether.

Further, the base of the poultice may contain one or more additivessuitably selected from among fillers such as kaolin, zinc oxide,titanium dioxide, talc, bentonite and synthetic aluminum silicate;antiseptics such as thymol, methyl paraben and ethyl paraben;antioxidants such as ascorbic acid, stearic esters,dibutylhydroxytoluene, butylhydroxyanisole, gallic esters, vitamin E,vitamin E acetate and disodium edetate; ultraviolet absorbers such as2-hydroxy-4-methoxybenzophenone, ethyl p-aminobenzoate,2-(2-hydroxy-5-methylphenyl)benzotriazole, glycol salicylate, methylsalicylate and phenyl salicyalte; and emulsifying agents such as fattyacid esters of sorbitan, fatty acid esters of glycerol, fatty acidesters of decaglycerol, fatty acid esters of polyoxyethylene sorbitan,fatty acid esters of polyethylene glycol and polyoxyethylene alkylethers.

It is essential that the support of the poultice is made of a materialwhich has no influence on the release of a drug, i.e., that the supportneither interacts with a drug nor adsorb a drug. The support is selectedfrom the group consisting of films and sheets of polyethylene,polypropylene, polyvinyl chloride, polyester, nylon and polyurethane;porous materials, expanded materials and woven and nonwoven fabrics ofthese polymers; laminates each comprising one or more members selectedfrom the group consisting of these films and sheets and one or moremembers selected from the group consisting of these materials andfabrics and so forth. The release sheet of the poultice according to thepresent invention may be selected from the group consisting of films ofpolyethylene, polypropylene and polyester; products of release treatmentof these films with silicone compounds; release paper and so forth.

The preparation of the poultice will now be described, though thepoultice can be easily prepared by known processes.

For example, a nonsteroidal anti-inflammatory agent selected from thegroup consisting of diclofenac, ketoprofen, flurbiprofen, tenidap,loxoprofen, ketorolac, felbinac, suprofen, indomethacin and esterderivatives and salts of these drugs is solubilized in3-l-menthoxypropane-1,2-diol to form a solution (A) which may, ifnecessary, be incorporated with one or more additives selected from thegroup consisting of a stabilizer, an antioxidant, an ultravioletabsorber, an emulsifying agent, an antiseptic, an antimicrobial and soforth. Separately, a water-soluble polymer is mixed into, dispersed andsolubilized in a polyhydric alcohol or water to form a homogeneous paste(B). The solution (A) is added to the paste (B) to form a homogeneousdispersion. This dispersion is spread directly on a support, oralternatively it is once spread on a paper or film treated with areleasing agent and thereafter transferred to a support by pressing.Thus, a poultice according to the present invention is prepared. Theabove-mentioned procedure for mixing base materials, a drug and othercomponents is just one example, not limiting the procedure for preparingthe poultice according to the present invention.

The plaster according to the present invention comprises, for example,(a) a nonsteroidal anti-inflammatory agent selected from the groupconsisting of diclofenac, ketoprofen, flurbiprofen, tenidap, loxoprofen,ketorolac, felbinac, suprofen and ester derivatives and salts of thesedrugs, (b) a solubilizer comprising a rosin ester derivative and3-l-menthoxypropane-1,2-diol, (c) a styrene-isoprene-styrene blockcopolymer or an acrylic adhesive as the base polymer and (d) a softeningagent or a known plaster base.

The support for the plaster is selected from among polypropyene fabricsand polyester fabrics which have no influence on the release of anonsteroidal anti-inflammatory agent. The polyester fabric to be used asthe support is preferably one made of polyethylene terephthalate (PET)or polybutylene terephthalate (PBT). In order to attain excellentrelease of a nonsteroidal anti-inflammatory agent, it is essential thatthe support neither interacts with a nonsteroidal anti-inflammatoryagent nor adsorb it. From this standpoint, the optimum polymerconstituting the support is polypropylene, PET or PBT. The use of asupport made of polypropylene, FET or PBT prevents the adsorption of adrug to the support to enable excellent release of the drug.

The plaster according to the present invention is provided with suchstretchability that the average stresses at 50% elongation in lengthwiseand widthwise directions each is 0.3 kg/cm or below, so that it can beapplied to a bend of human skin. By virtue of this stretchability, theplaster according to the present invention not only is capable to beused expediently and to follow the move of the skin so that the frictionand pressure during the use of the plaster on the skin decreases, thuscausing little side effects such as contact dermatitis.

The plaster according to the present invention is characterized by usinga mixture comprising a rosin ester derivative, which is well known bythose skilled in the art as a tackifier resin, and3-l-menthoxypropane-1,2-diol at a specific ratio so as to attainexcellent solubility of a drug surprisingly. Further, the use of thismixture improves the release of a drug remarkably. In order to attainmore excellent solubility of a drug such as a nonsteroidalanti-inflammatory agent in the base and more excellent release thereoffrom the base, it is preferable that a nonsteroidal anti-inflammatoryagent, a rosin ester derivative and 3-l-menthoxypropane-1,2-diol becontained at a weight ratio of 1:(2 to 25:(1 to 10). When thesecomponents are contained at such a ratio as above, the drug exhibitshigh solubility and releasability.

The term "rosin ester derivative" used in this specification refers toany of the products prepared by esterifying various rosins andsubjecting the obtained esters to hydrogenation or purification. Theesters include methyl ester, glycerol ester and pentaerythritol ester.The rosin ester derivatives include Ester Gum A, AA-G, H and HP (tradenames, products of Arakawa Chemical Industry Co, LTD.), Hariester-L, Sand P (trade names, products of Harima Chemicals, Inc.), Super EsterA-75 (trade name, a product of Arakawa Chemical Industry Co., Ltd.),KE-311 (trade name, a product of Arakawa Chemical Industry Co., Ltd.),Hercolyn D (trade name, a product of Hercules Inc.) and Foral 85 and 105(trade names, products of Hercules Inc.).

The base polymer of the plaster may be selected from conventional onesin consideration of safety For the skin, releasability of a drug andadhesion to the skin. From the standpoint of the release characteristicsof a nonsteroidal anti-inflammatory agent, it is preferable that thebase polymer be a styrene-isoprene-styrene block copolymer having aparticularly low polarity. Such block copolymers include CariflexTR-1107, TR-1111, TR-1112 and TR-1117 (trade names, products of ShellChemical) and Solprene 428 (trade name, a product of PhillipsPetroleum). These styrene-isoprene-styrene block copolymers may be eachused together with other polymer such as polyisobutylene. Vistanex(trade name, a product of Exxon Kagaku) is preferably used as thepolyisobutylene.

The softening agent serves to plasticize or soften thestyrene-isoprene-styrene block copolymer used as the base polymer tokeep the adhesion of the plaster to the skin at a proper level. Thesoftening agent may be selected from the group consisting of almond oil,olive oil, camellia oil, persic oil, peanut oil, liquid paraffin and soforth. The amount of the softening agent used is preferably 150 to 350parts by weight per 100 parts by weight of the styrene-isoprene-styreneblock copolymer.

The content of a drug is preferably 70 to 1200 μg/cm² from thestandpoints of therapeutically effective release of a drug andavailability thereof, though it is not particularly limited. Preferableproportions of a drug, rosin ester derivative,3-l-menthoxypropane-1,2-diol, styrene-isoprene-styrene block copolymerand softening agent are as follows.

That is, the plaster comprises 0.5 to 10% by weight of a drug, 5 to 70%by weight of a rosin ester derivative, 0.5 to 10% by weight of3-l-menthoxypropane-1,2-diol, 5 to 40% by weight of astyrene-isoprene-styrene block copolymer and 10 to 75% by weight of asoftening agent, each percentage being based on the total amount.

The plaster according to the present invention can be easily prepared byknown processes. For example, it can be prepared by mixing astyrene-isoprene-styrene block copolymer with a softening agent and arosin ester derivative under heating at 120° to 160° C. by the use of amixing machine such as kneader or mixer, adding a drug and3-l-menthoxypropane-1,2-diol to the obtained mixture, and applying theresulting mixture to a support either by spreading the mixture directlyon a woven or nonwoven fabric of polypropylene or polyester or byspreading the mixture on a paper or film treated with a releasing agentand thereafter transferring the spread mixture to a desired support bypressing.

Now, brief description will be made of other percutaneously absorbablepreparations (such as ointment, gel, cream, gel-type cream, lotion,reserver-type patch, liniment and aerosol) according to the presentinvention.

The ointment according to the present invention comprises at leasthigher fatty acid such as myristic acid or an ester thereof, a wax suchas spermaceti, a surfactant such as polyoxyethylene and a hydrocarbonsuch as hydrophilic vaseline in addition to a drug and3-l-menthoxypropane-1,2-diol.

The ointment can be prepared by, for example, mixing 5 to 15% by weightof a higher fatty acid or an ester thereof with 1 to 10% by weight of asurfactant, 0.5 to 10% by weight of a drug and 0.5 to 10% by weight of3-l-menthoxypropane-1,2-diol either at room temperature or underheating, adding 4 to 10% by weight of a wax and 50 to 90% by weight of ahydrocarbon to the obtained mixture, heating or heat-melting theresulting mixture, keeping the mixture at 50° to 100° C. to make thewhole mixture a transparent solution, homogenating the solution with ahomomixer, and lowering the temperature of the resulting solution toroom temperature under stirring.

The gel according to the present invention comprises at least a loweralcohol (such as ethanol), water, a gelling agent (such as carboxyvinylpolymer) and a neutralizing agent (such as triethanolamine) in additionto a drug and 3-l-menthoxypropane-1,2-diol.

The gel can be prepared, for example, as follows: 0.5 to 5% by weight ofa gelling agent is swollen with at most 55% by weight of water;separately, 0.5 to 10% by weight of a drug is solubilized in 0.5 to 10%by weight of 3-l-menthoxypropane-1,2-diol and the obtained solution isfurther solubilized in a mixture comprising at most 40% by weight of aglycol and at most 60% by weight of a lower alcohol; the obtainedsolution is mixed with the gelling agent swollen above; and theresulting mixture is adjusted to pH 4-7 by the addition of aneutralizing agent, thus forming a gel according to the presentinvention.

The cream according to the present invention comprises at least a higherfatty acid ester such as a myristate, water, a hydrocarbon such asliquid paraffin) and an emulsifying agent such as polyoxyethylene alkylether in addition to a drug and 3-l-menthoxypropane-1,2-diol.

The cream can be prepared by stirring a mixture comprising a drug,3-l-menthoxypropane-1,2-diol, a higher fatty acid ester, water, ahydrocarbon and an emulsifying agent in proper amounts.

A gel-type cream has intermediate properties between a gel and a creamand can be prepared by adding a gelling agent such as a carboxyvinylpolymer to components of cream as described above and adjusting theresulting mixture to pH 4-8, preferably pH 5-6.5 by the addition of aneutralizing agent such as diisopropanolamine.

The gel-type cream according to the present invention can be prepared,for example, as follows: 0.5 to 10% by weight of a drug is solubilizedin 0.5 to 10% by weight of 3-l-menthoxypropane-1,2-diol and the obtainedsolution is further solubilized in a mixture comprising at most 25% byweight of a higher fatty acid ester and at most 40% by weight of a loweralcohol, followed by the addition of at most 5% by weight of anemulsifying agent; separately, 0.5 to 5% by weight of a gelling agent isswollen with water; the swollen agent is mixed with the solutionprepared above; and the obtained mixture is homogenized with a homomixerand adjusted to pH 4-8 by the addition of a neutralizing agent.

The lotion according to the present invention comprises at least a loweralcohol such as ethanol and water and/or a glycol in addition to a drugand 3-l-menthoxypropane-1,2-diol.

The lotion can be prepared by stirring a mixture comprising a drug,3-l-menthoxypropane-1,2-diol, a lower alcohol and water and/or a glycolin proper amounts.

The reserver-type patch according to the present invention comprises atleast (1) a backing layer, (2) a drug reserving layer, (3) a drugreleasing layer and (4) a pressure-sensitive adhesive layer, wherein thebase of the drug reserving layer (2) comprises one mixture selected fromthe group consisting of

(a) mixture comprising at least a glycol, a lower alcohol, water and awater-soluble polymer,

(b) a mixture comprising at least an aliphatic alcohol and a polyhydricalcohol and

(c) a mixture comprising at least a paraffin and a silicon compound,

in addition to a drug and 3-l-menthoxypropane-1,2-diol.

The liniment according to the present invention comprises at least analcohol such as ethanol or polyethylene glycol, water and an ester offatty acid such as adipic acid or sebacic acid in addition to a drug and3-l-menthoxypropane-1,2-diol.

The liniment can be prepared by dissolving 0.5 to 10% by weight of adrug in 0.5 to 10% by weight of 3-l-menthoxypropane-1,2-diol and mixingthe obtained solution with 10 to 70% by weight of an alcohol, at most55% by weight of water and at most 60% by weight of a fatty acid esterunder stirring.

The aerosol according to the present invention comprises at least alower alcohol, water and dimethyl ether and/or liquefied petroleum gasin addition to a drug and 3-l-menthoxypropane-1,2-diol, and may furthercontain an auxiliary drug such as camphor α-tocopherol or menthol asneeded.

The aerosol can be prepared by dissolving 0.5 to 10% by weight of a drugin 0.5 to 10% by weight of 3-l-menthoxypropane-1,2-diol, adding a loweralcohol and water to the obtained solution, charging the obtainedmixture into an aerosol container and injecting dimethyl ether and/orliquefied petroleum gas as a propellant into the container.

The percutaneously absorbable preparations according to the presentinvention may further contain various pharmacologically acceptableadditives, so far as the object of the present invention is not marred.Examples of such additives include a stabilizer, an antioxidant, aperfume, a filler, an ultraviolet absorber, an antihistamine, anantiseptic, an antimicrobial agent and an absorbefacient.

Then, the pack according to the present invention will be described. Thepack according to the present invention is characterized by using3-l-menthoxypropane-1,2-diol as the solubilizer for a fat-soluble powderused as the pharmaceutically effective ingredient.

The term "fat-soluble powder" used in this specification refers to apowder which is insoluble or difficultly soluble in water, and such apowder includes pharmaceutically effective ingredients and variousadditives used in the preparation of the pack. In particular, it ispreferable that the powder be selected from the group consisting ofglycyrrhetinic acid, stearyl glycyrrhetinate, glycyrrhizinic acid,L-ascorbyl stearate, L-ascorbyl palmitate, calciferol, cholecalciferol,pionin and isopropylmethylphenol. The use of3-l-menthoxypropane-1,2-diol as the solubilizer for a fat-soluble powderas described above enables the stable dissolution of the powder in thebase to give an odorless pack imparting comfortable refreshingrefrigeration to the skin.

It is preferable that the content of 3-l-menthoxypropane-1,2-diol in thepack be in the range of 0.001 to 5% by weight. When the content is lessthan 0.001% by weight, no satisfactory solubilizability will beattained, while when it exceeds 5% by weight, the resulting pack will bepoor in physical properties and feelings in use.

The dosage form of the pack according to the present invention is notparticularly limited, but may be any conventional one selected from thegroup consisting of face cleasing packs of creamy, clayey and foamtypes, sheet packs of pressure-sensitive adhesive type and impregnationtype, peel-off pack (of film forming type) and so forth. Of course, thepack may further contain a conventional filler, perfume or the like atneed.

BRIEF DESCRIPTION OF DRAWING

FIGURE 1 is a graph showing the human absorption rates of the plastersof Example 9 and Comparative Example 6.

DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention will be better understood by Examples which shouldnot be construed as limiting the invention, in comparison withComparative Examples.

    ______________________________________                                        Example 1           poultice                                                  ______________________________________                                        (A)    3-l-menthoxypropane-1,2-diol                                                                   1.0% by weight                                               diclofenac       0.5% by weight                                        (B)    purified water   48.5% by weight                                              gelatin          8.0% by weight                                               kaolin           1.0% by weight                                               glycerol         35.0% by weight                                              polysodium acrylate                                                                            2.0% by weight                                               polyvinyl alcohol                                                                              3.0% by weight                                               aluminum hydroxide                                                                             1.0% by weight                                        ______________________________________                                    

The above ingredients were solubilized together and agitated so as toobtain a homogeneous paste. The paste was applied on a polypropylenenonwoven fabric with a speader to obtain a percutaneously absorbablepreparation layer having a thickness of 1 mm. Then, the preparationlayer was covered with a polypropylene film and cut into pieces eachhaving a predetermined size so as to obtain intended pharmaceuticalproducts.

    ______________________________________                                        Example 2           poultice                                                  ______________________________________                                        (A)   3-l-menthoxypropane-1,2-diol                                                                    2.0% by weight                                              loxoprofen        1.0% by weight                                              thymol            0.1% by weight                                        (B)   purified water    62.4% by weight                                             gelatin           3.0% by weight                                              titanium oxide    1.0% by weight                                              glycerol          25.0% by weight                                             polysodium acrylate                                                                             3.0% by weight                                              carboxymethyl cellulose                                                                         1.0% by weight                                              ethylene glycol diglycidyl ether                                                                1.0% by weight                                              sorbitan fatty acid ester                                                                       0.5% by weight                                        ______________________________________                                    

The above ingredients were solubilized together and agitated so as toobtain a homogeneous paste. The paste was applied on a polyesternonwoven fabric with a spreader to obtain a percutaneously absorbablepreparation layer having a thickness of 0.5 mm. Then, the preparationlayer was covered with a polyethylene film and cut into pieces eachhaving a predetermined size so as to obtain intended pharmaceuticalproducts.

    ______________________________________                                        Example 3           poultice                                                  ______________________________________                                        (A)    3-l-menthoxypropane-1,2-diol                                                                   3.0% by weight                                               ibuprofen        0.5% by weight                                               ethyl paraben    0.2% by weight                                        (B)    purified water   42.3% by weight                                              methoxyethylene anhydrous                                                                      5.0% by weight                                               maleic acid copolymer                                                         synthetic aluminium silicate                                                                   3.0% by weight                                               glycerol         40.0% by weight                                              polyacrylic acid 2.0% by weight                                               polyvinyl alcohol                                                                              2.5% by weight                                               calcium hydroxide                                                                              1.5% by weight                                        ______________________________________                                    

The above ingredients were solubilized together and agitated so as toobtain a homogeneous paste. The paste was applied on a polyurethane filmwith a spreader to obtain a percutaneously absorbable preparation layerhaving a thickness of 1 mm. Then, the preparation layer was covered witha polyurethane film and cut into pieces each having a predetermined sizethereby to obtain intended pharmaceutical products.

    ______________________________________                                        Example 4           poultice                                                  ______________________________________                                        (A)   3-l-menthoxypropane-1,2-diol                                                                    2.0% by weight                                              ketoprofen        0.5% by weight                                        (B)   purified water    36.0% by weight                                             N-vinylacetamide  5.0% by weight                                              glycerol          50.0% by weight                                             polyacrylic acid  3.0% by weight                                              carboxymethyl cellulose                                                                         1.0% by weight                                              magnesium metasilicate alminate                                                                 1.5% by weight                                              fatty acid esters of glycerol                                                                   1.0% by weight                                        ______________________________________                                    

The above ingredients were solubilized together and agitated so as toobtain a homogeneous paste. The paste was applied on a polyesternonwoven fabric with a spreader to obtain a percutaneously absorbablepreparation layer having a thickness of 1 mm. Then, the preparationlayer was covered with a polyester film and cut into pieces each havinga predetermined size so as to obtain intended pharmaceutical products.

    ______________________________________                                        Comparative Example 1                                                                          poultice                                                     ______________________________________                                        (A)     crotamiton   1.0% by weight                                                   suprofen     0.8% by weight                                           (B)     purified water                                                                             54.2% by weight                                                  gelatin      6.0% by weight                                                   bentonite    5.0% by weight                                                   glycerol     25.0% by weight                                                  sodium alginate                                                                            2.0% by weight                                                   polyethylene oxide                                                                         4.0% by weight                                                   aluminum sulfate                                                                           1.5% by weight                                                   fatty acid esters of                                                                       0.5% by weight                                                   polyethylene glycol                                                   ______________________________________                                    

The above ingredients were solubilized together and agitated thereby toobtain a homogeneous paste. The paste was applied on a polyvinylchloride with a spreader to obtain a percutaneously absorbablepreparation layer having a thickness of 0.3 mm. Then, the preparationlayer was covered with a polypropylene film and cut into pieces eachhaving a predetermined size thereby to obtain intended pharmaceuticalproducts.

    ______________________________________                                        Comparative Example 2                                                                             poultice                                                  ______________________________________                                        (A)   glycerol salicylate                                                                             2.0% by weight                                              ketoprofen        0.5% by weight                                        (B)   purified water    36.0% by weight                                             N-vinylacetamide  5.0% by weight                                              fatty acid esters of glycerol                                                                   1.0% by weight                                              glycerol          50.0% by weight                                             polyacrylic acid  3.0% by weight                                              carboxymethyl cellulose                                                                         1.0% by weight                                              magnesium metasilicate alminate                                                                 1.5% by weight                                        ______________________________________                                    

The above ingredients were solubilized together and agitated thereby toobtain a homogeneous paste. The paste was applied on a polyesternonwoven fabric with a spreader to obtain a percutaneously absorbablepreparation layer having a thickness of 1 mm. Then, the preparationlayer was covered with a polyester film and cut into pieces each havinga predetermined size thereby to obtain intended pharmaceutical products.

    ______________________________________                                        Comparative Example 3                                                                            poultice                                                   ______________________________________                                        (A)    butylene glycol 4.0% by weight                                                peppermint oil  1.0% by weight                                                loxoprofen      0.5% by weight                                         (B)    purified water  47.5% by weight                                               gelatine        3.0% by weight                                                kaolin          1.0% by weight                                                glycerol        35.0% by weight                                               polysodium acrylate                                                                           3.0% by weight                                                carboxyvinyl polymer                                                                          2.5% by weight                                                dextrin         2.0% by weight                                                sorbitan polyglycidyl ether                                                                   0.5% by weight                                         ______________________________________                                    

The above ingredients were solubilized together and agitated thereby toobtain a homogeneous paste. The paste was applied on a polypropylenenonwoven fabric with a spreader to obtain a percutaneously absorbablepreparation layer having a thickness of 1 mm. Then, the preparationlayer was covered with a polyester film and cut into pieces each havinga predetermined size thereby to obtain intended pharmaceutical products.

    ______________________________________                                        Example 5         plaster                                                     ______________________________________                                        styrene-isoprene-styrene                                                                        22.5% by weight                                             block copolymer                                                               polyisobutylene    5.0% by weight                                             tackifier (rosin ester)                                                                         15.0% by weight                                             liquid paraffin   56.0% by weight                                             3-l-menthoxypropane-1,2-diol                                                                     1.0% by weight                                             ketotifen          0.5% by weight                                             ______________________________________                                    

The above components were agitated under heating, thereby obtaining apaste. The paste was spread on a foundation to obtain a tape containingketotifen.

    ______________________________________                                        Example 6          plaster                                                    ______________________________________                                        pressure-sensitive adhesive of                                                                   77.0% by weight                                            acrylic resin solubilizer type                                                                   (in terms of solids)                                       (trade name: NISSETSU PE-300)                                                 3-l-menthoxypropane-1,2-diol                                                                     15.0% by weight                                            isosorbide dinitrate                                                                              8.0% by weight                                            ______________________________________                                    

The above components were mixed together to obtain a paste. The pastewas spread on a foundation and then freed of the solvent by evaporationthereby to obtain a tape containing isosorbide dinitrate.

    ______________________________________                                        Example 7          plaster                                                    ______________________________________                                        silicone adhesive  89.0% by weight                                            (trade name: BIO-PSA X7-2920)                                                                    (in terms of solids)                                       3-l-menthoxypropane-1,2-diol                                                                      7.0% by weight                                            clonidine           4.0% by weight                                            ______________________________________                                    

The above components were agitated and mixed together to obtain a paste.The paste was spread on a foundation and then freed of the solvent byevaporation thereby to obtain a tape containing clonidine.

    ______________________________________                                        Comparative Example 4                                                                            plaster                                                    ______________________________________                                        silicone adhesive  96.0% by weight                                            (trade name: BIO-PSA X7-2920)                                                                    (in terms of solids)                                       clonidine           4.0% by weight                                            ______________________________________                                    

The above components were mixed together under agitation to obtain apaste. The paste was spread on a foundation and then freed from thesolvent by evaporation thereby to obtain a tape containing clonidine.This Comparative Example indicates a formulation which was the same asExample 7 except for 4, 3-l-menthoxypropane-1,2-diol.

    ______________________________________                                        Comparative Example 5                                                                              plaster                                                  ______________________________________                                        silicone adhesive    89.0%   by weight                                        (trade name: BIO-PSA X7-2920)                                                                      (in terms of solids)                                     isopropyl myristate  7.0%    by weight                                        clonidine            4.0%    by weight                                        ______________________________________                                    

The above components were agitated and mixed together to obtain a paste.The paste was spread on a foundation and then freed of the solvent byevaporation thereby to obtain a tape containing clonidine. ThisComparative Example 5 indicates a formulation which was the same asExample 7 except that isopropyl myristate was substituted for thementhoxypropane-1,2-diol used in Example 7.

    ______________________________________                                        Example 8            plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           25.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      59.0%   by weight                                        rosin ester derivative                                                                             5.0%    by weight                                        (trade name: Ester Gum AA-G)                                                  3-l-menthoxypropane-1,2-diol                                                                       10.0%   by weight                                        diclofenac           1.0%    by weight                                        ______________________________________                                    

The components of the above prescription were mixed by a kneader toobtain a paste. Thereafter, the paste was applied directly on a PBTwoven fabric and then covered with a liner to obtain a plaster.

    ______________________________________                                        Example 9            plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           20.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      43.5%   by weight                                        polyisobutylene      10.0%   by weight                                        (trade name: Vistanex)                                                        rosin ester derivative                                                                             21.5%   by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       4.0%    by weight                                        diclofenac           1.0%    by weight                                        ______________________________________                                    

The components of the above prescription were mixed by a mixer to obtaina paste. The paste was applied on a plastic film previously endowed withreleasability and then covered with a PET woven fabric andpressure-contact transferred to obtain a plaster.

    ______________________________________                                        Example 10           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           21.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      63.0%   by weight                                        rosin ester derivative                                                                             10.0%   by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       4.0%    by weight                                        diclofenac           2.0%    by weight                                        ______________________________________                                    

The components of the above prescription were mixed together by akneader to obtain a paste. The paste was applied on a plastic filmpreviously endowed with releasability and, covered tereon with a PBTnonwoven fabric and pressure-contact transferred to obtain a plaster.

    ______________________________________                                        Example 11           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           30.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1111)                                                liquid paraffin      57.0%   by weight                                        rosin ester derivative                                                                             7.0%    by weight                                        (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                       5.0%    by weight                                        diclofenac           1.0%    by weight                                        ______________________________________                                    

The components of the above prescription were mixed together by akneader to obtain a paste. The paste was applied on a plastic filmpreviously endowed with releasability, thereon covered with apolypropylene nonwoven fabric and pressure-contact transferred to obtaina plaster.

    ______________________________________                                        Example 12           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           15.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene      5.0%    by weight                                        (trade name: Vistanex)                                                        liquid paraffin      23.0%   by weight                                        rosin ester derivative                                                                             42.0%   by weight                                        (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                       10.0%   by weight                                        diclofenac           5.0%    by weight                                        ______________________________________                                    

The components of the above prescription were mixed together by akneader to obtain a paste. The paste was applied on a plastic filmpreviously endowed with releasability, thereon covered with apolypropylene nonwoven fabric and pressure-contact transferred to obtaina plaster.

    ______________________________________                                        Example 13           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           18.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1112)                                                liquid paraffin      54.5%   by weight                                        rosin ester derivative                                                                             18.5%   by weight                                        (trade name: Foral 105)                                                       3-l-menthoxypropane-1,2-diol                                                                       6.0%    by weight                                        diclofenac methyl ester                                                                            3.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 8.

    ______________________________________                                        Example 14           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           25.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      68.0%   by weight                                        rosin ester derivative                                                                             5.0%    by weight                                        (trade name: Ester Gum AA-G)                                                  3-l-menthoxypropane-1,2-diol                                                                       1.5%    by weight                                        ketoprofen           0.5%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 15           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           20.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      43.5%   by weight                                        rosin ester derivative                                                                             30.5%   by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       3.0%    by weight                                        ketoprofen           3.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 16           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           15.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutene        7.0%    by weight                                        (trade name: Vistanex)                                                        liquid paraffin      23.0%   by weight                                        rosin ester derivative                                                                             40.0%   by weight                                        (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                       10.0%   by weight                                        ketoprofen           5.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 17           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           28.0%   by weight                                        block copolymer                                                               (trade name: Solprene 418)                                                    polybutene           5.0%    by weight                                        liquid paraffin      57.7%   by weight                                        rosin ester derivative                                                                             7.0%    by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       1.8%    by weight                                        flurbiprofen         0.5%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Example 18           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           21.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      66.8%   by weight                                        rosin ester derivative                                                                             7.2%    by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       4.0%    by weight                                        flurbiprofen         1.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 19           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           21.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      45.0%   by weight                                        rosin ester derivative                                                                             20.0%   by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       9.0%    by weight                                        flurbiprofen         5.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 20           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           11.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                styrene-isoprene-styrene                                                      block copolymer      11.0%   by weight                                        (trade name: Cariflex TR-1111)                                                liquid paraffin      44.0%   by weight                                        rosin ester derivative                                                                             26.0%   by weight                                        (trade name: Ester Gum AA-G)                                                  3-l-menthoxypropane-1,2-diol                                                                       7.0%    by weight                                        flurbiprofen         1.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Example 21           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           30.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      56.0%   by weight                                        rosin ester derivative                                                                             8.0%    by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       5.0%    by weight                                        loxoprofen           1.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 22           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           12.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1111)                                                liquid paraffin      28.0%   by weight                                        rosin ester derivative                                                                             40.0%   by weight                                        (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                       12.0%   by weight                                        loxoprofen           8.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 23           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           21.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1112)                                                liquid paraffin      50.0%   by weight                                        rosin ester derivative                                                                             20.5%   by weight                                        (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                       5.5%    by weight                                        loxoprofen           3.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Example 24           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           10.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1111)                                                liquid paraffin      43.0%   by weight                                        rosin ester derivative                                                                             35.0%   by weight                                        (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                       10.0%   by weight                                        sodium loxoprofen    2.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 25           plaster                                                  ______________________________________                                        styrene-isoprene-styrene                                                                           20.0%   by weight                                        block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin      47.0%   by weight                                        rosin ester derivative                                                                             21.0%   by weight                                        (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                       9.0%    by weight                                        sodium loxoprofen    3.0%    by weight                                        ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 26         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         22.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                polyisobutylene     5.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    52.0% by weight                                            rosin ester derivative                                                                           12.0% by weight                                            (trade name: Hercolyn D)                                                      3-l-menthoxypropane-1,2-diol                                                                      7.0% by weight                                            loxoprofen          2.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 27         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                liquid paraffin    38.0% by weight                                            rosin ester derivative                                                                           30.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      8.0% by weight                                            ketorolac           4.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 28         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         28.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin    57.5% by weight                                            rosin ester derivative                                                                            9.0% by weight                                            (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                      4.5% by weight                                            ketorolac           1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 29         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         21.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1112)                                                liquid paraffin    53.0% by weight                                            rosin ester derivative                                                                           10.0% by weight                                            (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                     14.0% by weight                                            ketorolac tromethamine                                                                            2.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Example 30         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         33.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                liquid paraffin    60.0% by weight                                            rosin ester derivative                                                                            5.0% by weight                                            (trade name: Foral 105)                                                       3-l-menthoxypropane-2,2-diol                                                                      1.5% by weight                                            ketorolac           0.5% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 31         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene     5.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    55.0% by weight                                            rosin ester derivative                                                                           10.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      8.0% by weight                                            ketoprofen          2.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 8.

    ______________________________________                                        Example 32         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         15.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene    14.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    38.0% by weight                                            rosin ester derivative                                                                           25.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-dioi                                                                      5.0% by weight                                            ketoprofen          3.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 33         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         22.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene     8.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    48.0% by weight                                            rosin ester derivative                                                                           14.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      8.0% by weight                                            ketorolac           2.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 34         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         15.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene    12.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    27.0% by weight                                            rosin ester derivative                                                                           38.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      4.0% by weight                                            ketorolac           4.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 35         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin    45.5% by weight                                            rosin ester derivative                                                                           30.5% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      3.0% by weight                                            felbinac            1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 36         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         15.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene    14.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    38.0% by weight                                            rosin ester derivative                                                                           26.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      5.0% by weight                                            felbinac            2.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Example 37         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         22.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                polyisobutylene     5.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    52.0% by weight                                            rosin ester derivative                                                                           12.0% by weight                                            (trade name: Hercolyn D)                                                      3-l-menthoxypropane-1,2-diol                                                                      7.0% by weight                                            felbinac            2.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 38         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         28.0% by weight                                            block copolymer                                                               (trade name: Solprene 418)                                                    polybutene          5.0% by weight                                            liquid paraffin    57.0% by weight                                            rosin ester derivative                                                                            7.5% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      2.0% by weight                                            suprofen            0.5% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Example 39         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                liquid paraffin    40.0% by weight                                            rosin ester derivative                                                                           34.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      4.0% by weight                                            suprofen            2.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 40         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                polyisobutylene     5.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    45.0% by weight                                            rosin ester derivative                                                                           20.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      9.0% by weight                                            estradiol           1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 8.

    ______________________________________                                        Example 41         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene    12.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    37.0% by weight                                            rosin ester derivative                                                                           20.0% by weight                                            (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                     10.0% by weight                                            estradiol           1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 42         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         22.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene     6.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    45.0% by weight                                            rosin ester derivative                                                                           23.0% by weight                                            (trade name: Foral 105)                                                       3-l-menthoxypropane-1,2-diol                                                                      3.0% by weight                                            progesterone        1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 43         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         15.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                polyisobutylene    10.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    39.0% by weight                                            rosin ester derivative                                                                           30.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      5.0% by weight                                            progesterone        1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 11.

    ______________________________________                                        Example 44         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene     5.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    47.0% by weight                                            rosin ester derivative                                                                           17.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                     10.0% by weight                                            norethisterone      1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Example 45         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1111)                                                polyisobutylene    11.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    25.0% by weight                                            rosin ester derivative                                                                           30.0% by weight                                            (trade name: Ester Gum H)                                                     3-l-menthoxypropane-1,2-diol                                                                     13.0% by weight                                            norethisterone      1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 10.

    ______________________________________                                        Example 46         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1112)                                                polyisobutylene    12.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    30.0% by weight                                            rosin ester derivative                                                                           30.0% by weight                                            (trade name: Foral 105)                                                       3-l-menthoxypropane-1,2-diol                                                                      7.0% by weight                                            testosterone        1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 9.

    ______________________________________                                        Example 47         plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         22.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                polyisobutylene     5.0% by weight                                            (trade name: Vistanex)                                                        liquid paraffin    45.0% by weight                                            rosin ester derivative                                                                           22.0% by weight                                            (trade name: KE-311)                                                          3-l-menthoxypropane-1,2-diol                                                                      5.0% by weight                                            testosterone        1.0% by weight                                            ______________________________________                                    

A plaster was obtained in the same manner as in Example 12.

    ______________________________________                                        Comparative Example 6                                                                            plaster                                                    ______________________________________                                        styrene-isoprene-styrene                                                                         20.0% by weight                                            block copolymer                                                               (trade name: Cariflex TR-1107)                                                liquid paraffin    43.5% by weight                                            polyisobutylene    10.0% by weight                                            (trade name: Vistanex)                                                        rosin ester derivative                                                                           21.5% by weight                                            (trade name: KE-311)                                                          diclofenac          1.0% by weight                                            ______________________________________                                    

The components of the above prescription were mixed by a mixer to obtaina paste. The paste was applied on a plastic film previously endowed withreleasability, thereon covered with polyester fabric andpressure-contact transferred to obtain a plaster. The prescription ofComparative Example 6 was the same as that of Example 9 except that theformer lacked in 3-l-menthoxy propane-1,2-diol as a solubilizer.

    ______________________________________                                        Example 48         ointment                                                   ______________________________________                                        white vaseline     76.0% by weight                                            glycerol monostearate                                                                            10.0% by weight                                            beef tallow        10.0% by weight                                            silicone oil        1.0% by weight                                            3-l-menthoxypropane-1,2-diol                                                                      2.0% by weight                                            flurbiprofen        1.0% by weight                                            ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare an ointment comprising flurbiprofen.

    ______________________________________                                        Example 49            ointment                                                ______________________________________                                        white vaseline        76.95%  by weight                                       diethyl sebacate      5.0%    by weight                                       spermaceti            5.0%    by weight                                       sodium polyoxyethylene-                                                                             4.0%    by weight                                       lauryletherphosphate                                                          2-hydroxy-4-methoxybenzophenone                                                                     1.0%    by weight                                       butyl p-oxybenzoate   0.05%   by weight                                       3-l-menthoxypropane-1,2-diol                                                                        5.0%    by weight                                       ketoprofen            3.0%    by weight                                       ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare an ointment comprising ketoprofen.

    ______________________________________                                        Example 50           ointment                                                 ______________________________________                                        white vaseline       82.95%  by weight                                        isopropyl myristate  8.0%    by weight                                        spermaceti           3.0%    by weight                                        sodium polyoxyethylene-                                                                            2.0%    by weight                                        lauryletherphosphate                                                          butyl p-oxybenzoate  0.05%   by weight                                        3-l-menthoxypropane-1,2-diol                                                                       3.0%    by weight                                        indomethacin         1.0%    by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare an ointment comprising indomethacin.

    ______________________________________                                        Example 51          gel                                                       ______________________________________                                        carboxyvinyl polymer                                                                               2.0% by weight                                           hydroxypropylcellulose                                                                             2.0% by weight                                           ethanol             37.0% by weight                                           purified water      33.0% by weight                                           propylene glycol    15.0% by weight                                           diisopropyladipate   2.0% by weight                                           diisopropanolamine   2.5% by weight                                           2-hydroxy-4-methoxybenzophenone                                                                    0.5% by weight                                           3-l-menthoxypropane-1,2-diol                                                                       3.0% by weight                                           ketoprofen           3.0% by weight                                           ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a gel comprising ketoprofen.

    ______________________________________                                        Example 52         gel                                                        ______________________________________                                        carboxyvinyl polymer                                                                              1.5% by weight                                            hydroxypropylcellulose                                                                            2.0% by weight                                            ethanol            17.0% by weight                                            purified water     35.3% by weight                                            propylene glycol   30.0% by weight                                            propylene carbonate                                                                              10.0% by weight                                            triethanolamine     0.2% by weight                                            3-l-menthoxypropane-1,2-diol                                                                      3.0% by weight                                            indomethacin        1.0% by weight                                            ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a gel comprising indomethacin.

    ______________________________________                                        Example 53         gel                                                        ______________________________________                                        carboxyvinyl polymer                                                                              1.0% by weight                                            ethanol            35.0% by weight                                            purified water     49.0% by weight                                            propylene glycol   10.0% by weight                                            diisopropanolamine  1.0% by weight                                            3-l-menthoxypropane-1,2-diol                                                                      3.0% by weight                                            flurbiprofen        1.0% by weight                                            ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a gel comprising flurbiprofen.

    ______________________________________                                        Example 54          cream                                                     ______________________________________                                        liquid paraffin     10.0% by weight                                           middle chain triacylglycerol                                                                       5.0% by weight                                           polyethylene glycol monostearate                                                                   3.0% by weight                                           glycerol             5.0% by weight                                           carboxyvinyl polymer                                                                               1.0% by weight                                           diisopropanolamine   0.4% by weight                                           methyl p-oxybenzoate                                                                               0.2% by weight                                           indomethacin         1.0% by weight                                           3-l-menthoxypropane-1,2-diol                                                                       5.0% by weight                                           purified water      residual quantity                                         ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a cream comprising indomethacin.

    ______________________________________                                        Example 55          cream                                                     ______________________________________                                        carboxyvinyl polymer                                                                              1.0% by weight                                            isopropyl myristate 5.0% by weight                                            ethanol             5.0% by weight                                            polyethylene glycol monostearate                                                                  1.0% by weight                                            coconut oil fatty acid                                                                            3.0% by weight                                            diethanolamide                                                                methyl p-oxybenzoate                                                                              0.2% by weight                                            2-hydroxy-4-methoxybenzophenone                                                                   0.8% by weight                                            ketoprofen          3.0% by weight                                            3-l-menthoxypropane-1,2-diol                                                                      7.0% by weight                                            purified water      residual quantity                                         ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a cream comprising ketoprofen.

    ______________________________________                                        Example 56         cream                                                      ______________________________________                                        carboxyvinyl polymer                                                                              1.0% by weight                                            glycerol           10.0% by weight                                            ethanol             5.0% by weight                                            diisopropanolamine  0.4% by weight                                            medium chain triglyceride                                                                         3.0% by weight                                            flurbiprofen        1.0% by weight                                            3-l-menthoxypropane-1,2-diol                                                                      5.0% by weight                                            purified water     residual quantity                                          ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a cream comprising flurbiprofen.

    ______________________________________                                        Example 57         gel-type cream                                             ______________________________________                                        carboxyvinyl polymer                                                                              1.0% by weight                                            isopropyl myristate                                                                              10.0% by weight                                            ethanol             5.0% by weight                                            polyethyleneglycol monostearate                                                                   1.0% by weight                                            methyl p-oxybenzoate                                                                              0.2% by weight                                            coconut oil fatty acid                                                                            3.0% by weight                                            diethanolamide                                                                ketoprofen          3.0% by weight                                            3-l-menthoxypropane-1,2-diol                                                                      3.0% by weight                                            purified water     residual quantity                                          ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a gel-type cream comprising ketoprofen.

    ______________________________________                                        Example 58         gel-type cream                                             ______________________________________                                        carboxyvinyl polymer                                                                             1.0% by weight                                             isopropyl palmitate                                                                              9.0% by weight                                             diethyl sebacate   9.0% by weight                                             polyoxyethylene cetylether                                                                       2.0% by weight                                             propylene carbonate                                                                              7.0% by weight                                             methyl p-oxybenzoate                                                                             0.2% by weight                                             sodium hydroxide   0.1% by weight                                             indomethacin       1.0% by weight                                             3-l-menthoxypropane-1,2-diol                                                                     5.0% by weight                                             purified water     residual quantity                                          ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a gel-type cream comprising indomethacin.

    ______________________________________                                        Example 59         gel-type cream                                             ______________________________________                                        carboxyvinyl polymer                                                                              1.5% by weight                                            cetyl isooctanoate 10.0% by weight                                            ethanol             5.0% by weight                                            polyethyleneglycol monostearate                                                                   1.0% by weight                                            methyl p-oxybenzoate                                                                              0.2% by weight                                            coconut oil fatty acid                                                                            3.0% by weight                                            diethanolamide                                                                flurbiprofen        3.0% by weight                                            3-l-menthoxypropane-1,2-diol                                                                      5.0% by weight                                            purified water     residual quantity                                          ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a gel-type cream comprising flurbiprofen.

    ______________________________________                                        Example 60         gel-type cream                                             ______________________________________                                        carboxyvinyl polymer                                                                             1.0% by weight                                             isopropyl myristate                                                                              6.0% by weight                                             diethyl sebacate   5.0% by weight                                             polyoxyethylene cethylether                                                                      2.0% by weight                                             propylene carbonate                                                                              3.0% by weight                                             methyl p-oxybenzoate                                                                             0.2% by weight                                             sodium hydroxide   0.1% by weight                                             ketorolac          3.0% by weight                                             3-l-menthoxypropane-1,2-diol                                                                     7.0% by weight                                             purified water     residual quantity                                          ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a gel-type cream comprising ketorolac.

    ______________________________________                                        Example 61           lotion                                                   ______________________________________                                        ethanol              57.0%   by weight                                        purified water       34.0%   by weight                                        propylene glycol     5.0%    by weight                                        3-l-menthoxypropane-1,2-diol                                                                       3.0%    by weight                                        ketoprofen           1.0%    by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a lotion comprising ketoprofen.

    ______________________________________                                        Example 62           lotion                                                   ______________________________________                                        ethanol              38.0%   by weight                                        purified water       50.0%   by weight                                        propylene glycol     6.0%    by weight                                        3-l-menthoxypropane-1,2-diol                                                                       5.0%    by weight                                        indomethacin         1.0%    by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a lotion comprising indomethacin.

    ______________________________________                                        Example 63           lotion                                                   ______________________________________                                        ethanol              30.0%   by weight                                        purified water       50.2%   by weight                                        propylene glycol     10.0%   by weight                                        methylcellulose      0.8%    by weight                                        3-l-menthoxypropane-1,2-diol                                                                       7.0%    by weight                                        flurbiprofen         2.0%    by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a lotion comprising flurbiprofen.

    ______________________________________                                        Example 64           reserver-type patch                                      ______________________________________                                        (1) a backing layer      polyester-type film                                  (2) a drug reserving layer                                                                             4 g of the following                                                          gel components were                                                           enclosed in the drug                                                          reserving layer.                                         ketorolac             5.0% by weight                                          3-l-menthoxypropane-1,2-diol                                                                        3.0% by weight                                          carboxyvinyl polymer  2.0% by weight                                          propylene glycol     30.0% by weight                                          triethyl citrate     19.0% by weight                                          purified water       39.4% by weight                                          2-hydroxy-4-methoxybenzophenone                                                                     0.5% by weight                                          diisopropanolamine    1.1% by weight                                      (3) a drug releasing layer                                                                             Juragard (trade name, a                                                       product of Polyplastic                                                        Co., Ltd.)                                           (4) a pressure-sensitive silicon-type adhesive                                    adhesive layer                                                            ______________________________________                                    

This reserver-type patch consisted of the above (1)-(4) layers and areleasing liner was put on the pressure-sensitive adhesive surfacethereby to obtain a laminate.

    ______________________________________                                        Example 65           reserver-type patch                                      ______________________________________                                        (1) a backing layer      polyester-type film                                  (2) a drug reserving layer                                                                             4 g of the following                                                          gel composition were                                                          enclosed in the drug                                                          reserving layer.                                         ketoprofen            3.0% by weight                                          3-l-menthoxypropane-1,2-diol                                                                        5.0% by weight                                          liquid paraffin      70.0% by weight                                          stearyl alcohol      20.0% by weight                                          d-limonene            2.0% by weight                                      (3) a drug releasing layer                                                                             Cotran (tradename, a                                                          product of 3M Co., Ltd.                              (4) a pressure-sensitive polyisobutylene-                                         adhesive layer       type adhesive                                        ______________________________________                                    

This reserver-type patch consisted of the above (1)-(4) layers and areleasing liner was put on the pressure-sensitive adhesive surfacethereby to obtain a laminate.

    ______________________________________                                        Example 66             reserver-type patch                                    ______________________________________                                        (1)   a backing layer      Aluminum laminating                                                           polyester film                                     (2)   a drug reserving layer                                                                             4 g of the following                                                          gel composition were                                                          enclosed in the drug                                                          reserving layer.                                         ketorolac            5.0% by weight                                           3-l-menthoxypropane-1,2-diol                                                                       10.0% by weight                                          silicon              80.0% by weight                                          glycerol monolaurate 5.0% by weight                                     (3)   a drug releasing layer                                                                             Cotran                                             (4)   a pressure-sensitive silicon-type adhesive                                    adhesive layer       (around a support)                                 ______________________________________                                    

This reserver-type patch consisted of the above (1)-(4) layers and areleasing liner was put on the pressure-sensitive adhesive surfacethereby to obtain a laminate.

    ______________________________________                                        Example 67             reserver-type patch                                    ______________________________________                                        (1)   a backing layer      Aluminum laminating                                                           polyester film                                     (2)   a drug reserving layer                                                                             4 g of the following                                                          gel composition were                                                          enclosed in the drug                                                          reserving layer.                                         ketorolac            5.0% by weight                                           3-l-menthoxypropane-1,2-diol                                                                       10.0% by weight                                          silicon              80.0% by weight                                          glycerol monolauric acid                                                                           5.0% by weight                                     (3)   a drug releasing layer                                                                             Cotran                                             (4)   a pressure-sensitive silicon-type adhesive                                    adhesive layer       (around a support)                                 ______________________________________                                    

This reserver-type patch consisted of the above (1)-(4) layers and areleasing liner was put on the pressure-sensitive adhesive surface toobtain a laminate.

    ______________________________________                                        Example 68             reserver-type patch                                    ______________________________________                                        (1)   a backing layer      Aluminum laminating                                                           polyester film                                     (2)   a drug reserving layer                                                                             4 g of the following                                                          gel composition were                                                          enclosed in the drug                                                          reserving layer.                                         tulobuterol hydrochloride                                                                           5.0% by weight                                          3-l-menthoxypropane-1,2-diol                                                                        5.0% by weight                                          stearyl alcohol      10.0% by weight                                          cetyl alcohol        10.0% by weight                                          behenyl alcohol      10.0% by weight                                          propylene glycol     20.0% by weight                                          1,3-butylene glycol  35.0% by weight                                          lauryl alcohol        5.0% by weight                                    (3)   a drug releasing layer                                                                             Cotran                                             (4)   a pressure-sensitive silicon-type adhesive                                    adhesive layer       (around a support)                                 ______________________________________                                    

This reserver-type patch consisted of the above (1)-(4) layers and areleasing liner was put on the pressure-sensitive adhesive surface toobtain a laminate.

    ______________________________________                                        Example 69            liniment                                                ______________________________________                                        ethanol               45.0%   by weight                                       2-hydroxy-4-methoxybenzophenone                                                                     0.6%    by weight                                       diisopropyl adipate   30.0%   by weight                                       α-tocopherol    1.0%    by weight                                       hydroxypropylcellulose                                                                              1.5%    by weight                                       ketoprofen            2.0%    by weight                                       3-l-menthoxypropane-1,2-diol                                                                        4.0%    by weight                                       purified water        15.9%   by weight                                       ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a lotion comprising ketoprofen.

    ______________________________________                                        Example 70            liniment                                                ______________________________________                                        propyleneglycol       10.0%   by weight                                       2-hydroxy-4-methoxybenzophenone                                                                     0.2%    by weight                                       polyethyleneglycol    10.0%   by weight                                       monolaurate                                                                   crotamiton            0.5%    by weight                                       acetone               18.0%   by weight                                       ethyl alcohol         20.0%   by weight                                       ethanol               28.8%   by weight                                       ketoprofen            0.5%    by weight                                       3-l-menthoxypropane-1,2-diol                                                                        2.0%    by weight                                       purified water        10.0%   by weight                                       ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a liniment comprising ketoprofen.

    ______________________________________                                        Example 71            liniment                                                ______________________________________                                        polyethyleneglycol 400                                                                              45.0%   by weight                                       2-hydroxy-4-methoxybenzophenone                                                                     0.5%    by weight                                       α-tocopherol    1.0%    by weight                                       isopropylalcohol      31.5%   by weight                                       ethanol               40.0%   by weight                                       ketorolac             5.0%    by weight                                       3-l-menthoxypropane-1,2-diol                                                                        7.0%    by weight                                       purified water        7.0%    by weight                                       ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a liniment comprising ketorolac.

    ______________________________________                                        Example 72            liniment                                                ______________________________________                                        polyethyleneglycol    15.0%   by weight                                       monolaurate                                                                   2,2-hydroxy-4-methoxybenzophenone                                                                   0.7%    by weight                                       diisopropyl adipate   4.0%    by weight                                       α-tocopherol    1.0%    by weight                                       8-acetylsucrose denatured alcohol                                                                   49.6%   by weight                                       ketorolac             3.0%    by weight                                       3-l-menthoxypropane-1,2-diol                                                                        5.0%    by weight                                       purified water        21.7%   by weight                                       ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a liniment comprising ketorolac.

EXAMPLE 73 Aerosol

4.5% by weight of camphor, 4.0% by weight of3-l-menthoxypropane-1,2-diol, 3.0% by weight of ketoprofen and 1.0% byweight of 2-hydroxy-4-methoxybenzophenone were solubilized in 32.5% byweight of ethanol, incorporated with 26.0% by weight of water, chargedinto an aerosol container and then incorporated with 4.0% by weight oftalc to prepare a pharmaceutical solution, after which a mixedpropellant composed of 13.0% by weight of dimethyl ether and 12.0% byweight of liquefied petroleum gas was injected into the container,thereby to obtain an anti-inflammatory and analgetic aerosol. The aboveweight percentages were respectively based on the whole quantity.

EXAMPLE 74 Aerosol

4.5% by weight of camphor, 0.4% by weight of diphenhydramine, 5.0% byweight of 3-l-menthoxypropane-1,2-diol, 1.0% by weight of ketorolac and1.0% by weight of α-tocopherol were solubilized in 30.1% by weight ofethanol, incorporated with 24.0% by weight of water to the obtainedsolution, and then charged into an aerosol container, after which amixed propellant composed of 25.0% by weight of dimethyl ether and 9.0%by weight of liquefied petroleum gas was injected into the container,thereby to obtain an anti-inflammatory and analgetic aerosol, whereinthe ratios were respectively based on the whole quantity.

    ______________________________________                                        Example 75           creamy-type pack                                         ______________________________________                                        liquid paraffin      10.0%   by weight                                        cetanol              1.0%    by weight                                        sorbitan monostearate                                                                              3.0%    by weight                                        POE (20) sorbitan monostearate                                                                     3.0%    by weight                                        1,3-butylene glycol  5.0%    by weight                                        glycerol             3.0%    by weight                                        methyl paraben       0.2%    by weight                                        stearyl glycyrrhetinate                                                                            0.1%    by weight                                        3-l-menthoxypropane-1,2-diol                                                                       1.0%    by weight                                        purified water       73.7%   by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a cream-type pack.

    ______________________________________                                        Example 76           clay-type pack                                           ______________________________________                                        kaolin               20.0%   by weight                                        talc                 8.0%    by weight                                        glycerol             3.0%    by weight                                        propylene glycol     3.0%    by weight                                        carboxymethyl cellulose                                                                            0.3%    by weight                                        POE (20) sorbitan monooleate                                                                       2.0%    by weight                                        methyl paraben       0.1%    by weight                                        L-ascorbyl stearate  0.2%    by weight                                        3-l-menthoxypropane-1,2-diol                                                                       3.0%    by weight                                        purified water       60.4%   by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a clay-type pack.

    ______________________________________                                        Example 77           foam-type pack                                           ______________________________________                                        stearic acid         5.0%    by weight                                        behenic acid         5.0%    by weight                                        cetanol              1.0%    by weight                                        squalane             4.0%    by weight                                        glycerol             15.0%   by weight                                        POE (40) monostearate                                                                              1.0%    by weight                                        ethyl paraben        0.1%    by weight                                        L-ascorbyl palmitate 0.05%   by weight                                        3-l-menthoxypropane-1,2-diol                                                                       0.5%    by weight                                        purified water       68.35%  by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toprepare a liquid. Thereafter the liquid was injected with a liquefiedpetroleum gas into a container to obtain a foam-type pack.

    ______________________________________                                                             pressure-sensitive ad-                                   Example 78           hesive-type sheet pack                                   ______________________________________                                        gelatin              8.0%     by weight                                       glycerol             25.0%    by weight                                       sorbitol             7.0%     by weight                                       sodium polyacrylate  2.0%     by weight                                       polyvinyl alcohol    2.0%     by weight                                       aluminium hydroxide  1.0%     by weight                                       methyl paraben       0.05%    by weight                                       isopropyl methylphenol                                                                             0.01%    by weight                                       3-l-menthoxypropane-1,2-diol                                                                       0.005%   by weight                                       purified water       54.935%  by weight                                       ______________________________________                                    

The above components were mixed together under agitation, thereby toobtain a paste. The paste was spread on a nonwoven fabric, coveredthereon with a release film to obtain a laminate. The laminate was cutinto pieces each having a predetermined form to obtain adhesive-typesheet packs.

    ______________________________________                                                             impregnation-type                                        Example 78           sheet pack                                               ______________________________________                                        glycerol             10.0%   by weight                                        1,3-butylene glycol  10.0%   by weight                                        sodium hyaluroniate  0.1%    by weight                                        methyl paraben       0.1%    by weight                                        glycyrrhizinic acid  0.01%   by weight                                        3-l-menthoxypropane-1,2-diol                                                                       0.05%   by weight                                        purified water       79.74%  by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toobtain a mixture. The mixture was impregnated into a nonwoven fabric,covered thereon with a release film to obtain a laminate. The laminatewas cut into pieces each having a predetermined form to obtainimpregnation-type sheet packs.

    ______________________________________                                        Example 80           peel-off pack                                            ______________________________________                                        polyvinyl alcohol    20.0%   by weight                                        carboxymethyl cellulose                                                                            3.0%    by weight                                        titanium oxide       8.0%    by weight                                        1,3-butylene glycol  5.0%    by weight                                        squalane             3.0%    by weight                                        POE (10) nonylphenyl ether                                                                         0.5%    by weight                                        methyl paraben       0.1%    by weight                                        calciferol           0.01%   by weight                                        3-l-menthoxypropane-1,2-diol                                                                       0.1%    by weight                                        purified water       60.29%  by weight                                        ______________________________________                                    

The above components were mixed together under agitation, thereby toobtain peel-off packs.

COMPARATIVE EXAMPLE 7 Cream-type Pack

The procedure of Example 75 was followed except that the3-l-menthoxypropane-1,2-diol was not used, thereby to obtain acream-type pack.

COMPARATIVE EXAMPLE 8 Adhesive-type Sheet Pack

The procedure of Example 78 was followed except that the3-l-menthoxypropane-1,2-diol was not used, thereby to obtain aadhesive-type sheet pack.

TEST EXAMPLE 1

The plasters of Example 7 and Comparative Examples 4 and 5 were storedat 5° C. for two weeks, while they were observed with the lapse of timeto find whether the drug crystallized or not. The results are given inTable 1.

                  TABLE 1                                                         ______________________________________                                        Sample   initial  1 day  3 days  7 days                                                                              14 days                                ______________________________________                                        plaster  ∘                                                                          ∘                                                                        ∘                                                                         ∘                                                                       ∘                          of Ex. 7                                                                      plaster  x        x      x       x     x                                      of Comp.                                                                      Ex. 4                                                                         plaster  ∘                                                                          x      x       x     x                                      of Comp.                                                                      Ex. 5                                                                         ______________________________________                                         ∘: no crystallization was found                                   x: crystallization was found                                             

As apparent from the above results, the plaster of Example 7 containing3-l-menthoxypropane-1,2-diol as the solubilizer contained clonidine inits solubilized state in the base even after the lapse of two weeks,while the plaster of Comparative Example 4 containing no solubilizer andthat of Comparative Example 5 containing isopropyl myristate sufferedfrom the crystallization of clonidine in their respective bases. Thus,the above results supported the usefulness of3-l-menthoxypropane-1,2-diol as the solubilizer for clonidine.

TEST EXAMPLE 2 (Adhesion Test)

The poultices of Examples 1 to 4 and Comparative Examples 1 to 3 wereexamined for their adhesion and changes thereof time according to theNichiban Rolling Ball method. This method is such that a ball is sorolled along a poultice sample from a predetermined height at an angleof 30° C. as to draw a sine curve, to measure a distance from a pointwhere the rolling ball reaches the smple to a point where it stopsrolling. Accordingly, a shorter distance of roll or a bigger ball meansa more excellent adhesion. In this test, a poultice sample having alength of 140 mm was spread with its adhesive side up and a stainlesssteel ball (20/32 inch, JIS) was rolled along the sample to determinethe distance of roll of the ball. The results are given in Table 2.

                  TABLE 2                                                         ______________________________________                                        Pressure-                After storage                                        sensitive     Initial    for 6 months at                                      Adhesive tape adhesion (mm)                                                                            40° C. (mm)                                   ______________________________________                                        Ex. 1         50         48                                                   Ex. 2         30         33                                                   Ex. 3         35         38                                                   Ex. 4         43         41                                                   Comp. Ex. 1   98         95                                                   Comp. Ex. 2   78         82                                                   Comp. Ex. 3   passed through                                                                           passed through                                       ______________________________________                                    

As apparent from the above results, the polutices of Examples 1 to 4exhibited excellent adhesion and the adhesion did not change even afterthe lapse of time.

TEST EXAMPLE 3 (Test on Safety for the Skin)

The poultices of Examples 1 to 4 and Comparative Examples 1 to 3 wereexamined for safety for the skin.

The safety of each poultice for the skin was determined by 25 healthymale and female subjects according to the 48-hour closed patch test. Thechange in the skin of each subject was determined by observation 1 and24 hours after the peeling of the patch, and the irritativeness of thepoultice was evaluated according to the following criteria. The resultsare given in Tables 3 and 4.

-: no change in the skin

±: slight rubefaction

+: clear rubefaction

++: heavy contact dermatitis

                  TABLE 3                                                         ______________________________________                                        Time                                                                          which has                                 Rate (%) of                         elapsed                                   positive                            after  Judgement                   Total  reaction                            peeling                                                                              Sample    ++    +   ±                                                                              -   (subjects)                                                                           (±, + and ++)                    ______________________________________                                        1 hr   Ex. 1     0     0   0   25  25     0.0                                 1 hr   Ex. 2     0     0   1   24  25     4.0                                 1 hr   Ex. 3     0     0   0   25  25     0.0                                 1 hr   Ex. 4     0     0   0   25  25     0.0                                 1 hr   Comp. Ex. 1                                                                             0     0   2   23  25     8.0                                 1 hr   Comp Ex. 2                                                                              0     0   1   24  25     4.0                                 1 hr   Comp Ex. 3                                                                              0     0   3   22  25     12.0                                ______________________________________                                    

                  TABLE 4                                                         ______________________________________                                        Time                                                                          which has                                 Rate (%) of                         elapsed                                   positive                            after  Judgement                   Total  reaction                            peeling                                                                              Sample    ++    +   ±                                                                              -   (subjects)                                                                           (±, + and ++)                    ______________________________________                                        24 hrs Ex. 1     0     0   0   25  25     0.0                                 24 hrs Ex. 2     0     0   0   25  25     0.0                                 24 hrs Ex. 3     0     0   0   25  25     0.0                                 24 hrs Ex. 4     0     0   0   25  25     0.0                                 24 hrs Comp. Ex. 1                                                                             0     0   1   24  25     4.0                                 24 hrs Comp Ex. 2                                                                              0     0   0   25  25     0.0                                 24 hrs Comp Ex. 3                                                                              0     0   1   24  25     4.0                                 ______________________________________                                    

As apparent from the above results, the poultices of Examples 1 to 4exhibited extremely high safety for the skin.

TEST EXAMPLE 4 (Test on Human Percutaneous Absorption)

The poultices of Example 4 and Comparative Example 2 were each die-cutinto samples (3×3 cm²). These samples were applied to the upper backs ofeight healthy subjects respectively. After 8 hours, the samples werepeeled and examined for the amount of ketoprofen remaining in the peeledsamples by HPLC (high performance liquid chromatography). Thecalculation of human absorption rate, the determination of amount of theremaining ketoprofen and HPLC were conducted as follows:

(1) human absorption rate

=(1--remaining amount/initial content)×100

(2) determination of amount of residue of ketoprofen Each peeled samplewas extracted with 70 ml of methanol under reflux and the extract wasdiluted with methanol to 100 ml. The resulting dilution was used as thesample for HPLC.

(3) Conditions of HPLC

mobile phase; 0.2% aqueous solution of acetic acid:acetonitrile=55:45

detection wavelength; 254 nm

column; TSK gel ODS-80TM

flow rate; 1.0 μl/min.

                  TABLE 5                                                         ______________________________________                                                  Human absorption rate (%)                                           ______________________________________                                        Ex. 4       12.7                                                              Comp. Ex. 2 5.0                                                               ______________________________________                                    

As shown in Table 5, the poultice of Example 4 containing3-l-menthoxypropane-1,2-diol as the solubilizer exhibited a higherabsorption rate than that of the poultice of Comparative Example 2.

TEST EXAMPLE 5

The plasters of Example 9 and Comparative Example 6 were stored at 5°C., while they were observed with the lapse of time to determine whethercrystallization occurred or not. The results are given in Table 6.

                  TABLE 6                                                         ______________________________________                                        Sample  initial  1 day  3 days  7 days                                                                              14 days                                 ______________________________________                                        Ex. 9   ∘                                                                          ∘                                                                        ∘                                                                         ∘                                                                       ∘                           Comp. Ex. 6                                                                           ∘                                                                          ∘                                                                        x       x     x                                       ______________________________________                                         ∘: no crystallization was found                                   x: crystallization was found                                             

As apparent from the results given in Table 6, the plaster of Example 9contained diclofenac in a solubilized state in the base even after thelapse of time, though that of Comparative Example 6 containing nosolubilizer suffered from the crystallization of diclofenac. Thus, theabove results supported the usefulness of 3-l-menthoxypropane-1,2-diolas the solubilizer for diclofenac.

TEST EXAMPLE 6 (Test on Human Pecutaneous Absorption)

The plasters of Example 9 and Comparative Example 6 were each die-cutinto samples (3×3 cm²). These samples were applied to the upper backs ofsix healthy subjects respectively. After 8 hours, the samples werepeeled and examined for the residual amount of diclofenac by HPLC. Thecalculation of human absorption rate, the determination of residualamount of diclofenac and HPLC were conducted as follows:

(1) human absorption rate

=(1--residual amount/initial content)×100

(2) determination of residual amount of diclofenac:

Each peeled sample was subjected to ultrasonic extraction with 30 ml oftetrahydrofuran for 2 hours and the extract was diluted withtetrahydrofuren to 50 ml. The resulting dilution was used as the samplefor HPLC.

(3) Conditions of HPLC

mobile phase; 0.2% aqueous solution of acetic acid:acetonitrile=1:1

detection wavelength; 275 nm

column; TSK gel ODS-80TM

flow rate; 1.0 μl/min.

The results are given in FIGURE 1. As apparent from FIGURE 1, theplaster of Example 9 exhibited a significantly enhanced absorption rateas compared with that of Comparative Example 6. In other words, theplaster of Example 9 could contain diclofenac in a solubilized state byvirtue of the solubilizability of 3-l-menthoxypropane-1,2-diol therebyto give excellent release of diclofenac.

TEST EXAMPLE 7

The packs of Examples 75 and 78 and Comparative Examples 7 and 8 werestored at 5° C. for two weeks, while they were observed with the lapseof time to determine whether the fat-soluble powder crystallized or not.The results are given in Table 7.

                  TABLE 7                                                         ______________________________________                                        initial      1 day  3 days    7 days                                                                              14 days                                   ______________________________________                                        Ex. 75  ∘                                                                          ∘                                                                        ∘                                                                         ∘                                                                       ∘                           Ex. 78  ∘                                                                          ∘                                                                        ∘                                                                         ∘                                                                       ∘                           Comp. Ex. 7                                                                           x        x      x       x     x                                       Comp. Ex. 8                                                                           ∘                                                                          x      x       x     x                                       ______________________________________                                         ∘: no crystallization was found                                   x: crystallization was found                                             

The above results supported the usefulness of3-l-menthoxypropane-1,2-diol as the solubilizer for a fat-solublepowder.

TEST EXAMPLE 8

The packs of Example 75 and Comparative Example 7 were examinedorganoleptically by ten female subjects. The results are given in Table8.

                  TABLE 8                                                         ______________________________________                                                         Ex. 75                                                                              Comp. Ex. 7                                            ______________________________________                                        Odor       observed    0       0                                                         not observed                                                                              10      10                                             Refreshing observed    10      0                                              effect     not observed                                                                              0       10                                             Irritation observed    0       0                                              to the skin                                                                              not observed                                                                              10      10                                             Stickiness observed    0       1                                                         not observed                                                                              10      9                                              Roughness  observed    1       8                                                         not observed                                                                              9       2                                              ______________________________________                                    

It can be understood from the above results that the pack of Example 75has refreshing or refrigerant effect and is freed from thecrystallization of a fat-soluble powder thereby to be excellent infeelings in use.

Industrial Applicability

According to the present invention, 3-l-menthoxypropane-1,2-diol whichhas been used as a refrigerant is used as a solubilizer for apharmaceutically effective ingredient and this compound exhibits highsolubilizability for a pharmaceutically effective ingredient and isexcellent in safety, stability and compatibility. Accordingly, apercutaneously absorbable preparation (which is one of externalpreparations) containing said compound is improved in the release of apharmaceutically effective ingredient from the base and the pecutaneousabsorption of the effective agent. Further, such a preparation causeslittle side effects such as contact dermatitis even when appliedrepeatedly and is not irritant to the skin thereby to be extremely safe.Furthermore, the preparation is odorless and can impart comfortablerefreshing refrigeration to the skin.

Accordingly, the external preparation of the present invention is suitedfor percutaneously absorbable preparations and packs, thus having highindustrial applicability.

What is claimed is:
 1. A percutaneously absorbable preparation whichcomprises, by weight, 0.001 to 20% of 3-l-menthoxypropane-1,2-diol as asolubilizer for a drug and 0.001 to 20% of said drug, the balance beingother ingredients as adjuvants for said preparation.
 2. The preparationaccording to claim 1 wherein the content of 3-l-menthoxypropane-1,2-diolis 0.1 to 20% by weight.
 3. The preparation according to claim 1 whichis in a form selected from the group consisting of a poultice, aplaster, an ointment, a gel, a cream, a gel cream, a lotion, a reservoirpatch, a liniment and an aerosol.
 4. The preparation according to claim3 which is a poultice wherein said balance comprises a water-solublepolymer, a polyhydric alcohol and water.
 5. The preparation according toclaim 3 which is a plaster wherein said balance comprises a) a memberselected from the group consisting of a rosin ester, astyrene-isoprene-styrene block copolymer and an acrylic adhesive and (b)a softening agent, in the amount of 150-350 parts by weight per 100parts of said styrene-isoprene-styrene block copolymer, the amounts byweight of said drug, said rosin ester and said3-l-menthoxy-propane-1,2-diol being 1:(2 to 25):1 to (10).
 6. Thepreparation according to claim 3 which is an ointment wherein saidbalance comprises a higher fatty acid or an ester thereof, a wax, asurfactant a vaseline, and liquid paraffin.
 7. The preparation accordingto claim 3 which is a gel, wherein said balance comprises a loweralcohol, water, a gelling agent and a neutralizing agent.
 8. Thepreparation according to claim 3 which is a cream wherein said balancecomprises a higher fatty acid ester, water, a hydrocarbon which is avaseline, or liquid paraffin and an emulsifying agent.
 9. Thepreparation according to claim 3 which is a gel cream wherein saidbalance comprises a higher fatty acid ester, a lower alcohol, water,liquid paraffin, an emulsifying agent, a neutralizing agent and agelling agent.
 10. The preparation according to claim 3 which is alotion wherein said balance comprises a lower alcohol, water and aglycol.
 11. The preparation according to claim 3 which is a reservoirpatch which comprises (1) a backing layer; 2) a drug reservoir layer; 3)a drug releasing layer; 4) a pressure-sensitive adhesive layer, saiddrug-reservoir layer 2) has said 3-l-menthoxy propane-1,2-diol and abase, said base comprises (a) a mixture comprising a glycol, a loweralcohol, water and a water-soluble polymer; (b) a mixture comprising analiphatic monohydric alcohol or a polyhydric alcohol or both amonohydric alcohol and a polyhydric alcohol or (c) a mixture comprisingparaffin and a silicon compound.
 12. The preparation according to claim3 which is a liniment wherein said balance comprises an alcohol, waterand a fatty acid ester.
 13. The preparation according to claim 3 whichis an aerosol wherein said balance comprises a lower alcohol, water,dimethyl ether or liquefied petroleum gas or both dimethyl ether andliquefied petroleum gas.
 14. The preparation as set forth in claim 4which comprises, by weight, 0.1 to 20% of said solubilizer, 0.5 to 10%of said drug, 1-30% of a water-soluble polymer, 10 to 90% of apolyhydric alcohol and 10 to 90% of water.
 15. The plaster according toclaim 5 which comprises, by weight, 0.5 to 10% of3-l-menthoxypropane-1,2-diol, 0.5 to 10% of said drug, 5 to 70% of saidrosin ester, 5 to 40% of said styrene-isoprene-styrene block copolymerand 10-75% of said softening agent.
 16. The ointment according to claim6 which comprises, by weight, 0.5-10% of 3-l-menthoxypropane 1,2-diol,0.5-10% of said drug, 5-15% of said higher fatty acid or the esterthereof, 4-10% of said wax, 1 to 10% of said surfactant and 50-90% ofsaid hydrophilic vaseline.
 17. The ointment according to claim 16wherein said higher fatty acid is myristic acid and the ester of saidhigher fatty acid is glycerol monostearate, isopropyl myristate ordiethyl sebacate, said wax is selected from the group consisting ofspermaceti and beef tallow, and said hydrocarbon is hydrophilicvaseline.
 18. The gel according to claim 7 which comprises, by weight,0.5 to 10% of 3-l-menthoxypropane-1,2-diol, 0.5 to 10% of the drug, 0.5to 5% of said gelling agent, at the most 60% of the lower alcohol, atthe most 40% of the glycol, 0.2 to 2.5% of the neutralizing agent and atthe most 55% of water.
 19. The gel according to claim 18 wherein saidgelling agent is a carboxyvinyl polymer, said lower alcohol is ethanol,and said neutralizing agent is triethanolamine or diisopropanolamine.20. The gel cream according to claim 9 which comprises, by weight, 0.5to 10% of 3-l-menthoxypropane-1,2-diol, 0.5 to 10% of said drug, at most25% of the higher fatty acid ester, at most 40% of the lower alcohol, atmost 5% of said emulsifying agent, 0.5 to 5% of said gelling agent, thebalance being purified water.
 21. The gel-like cream according to claim20 wherein said higher fatty acid ester is isopropyl myristate,isopropyl palmitate or polyethylene glycol monostearate, said loweralcohol is ethanol, said gelling agent is a carboxyvinyl polymer, andsaid neutralizing agent is triethanolamine or diisopropanolamine. 22.The lotion according to claim 10 wherein said lower alcohol is ethanoland said glycol is propylene glycol.
 23. The liniment according to claim12 which comprises, by weight, 0.5 to 10% of said3-l-menthoxypropane-1,2-diol, 0.5 to 10% of said drug, 10 to 70% of saidalcohol, at most 55% of water and at most 60% of said fatty acid ester.24. The liniment according to claim 23 wherein said alcohol is ethanol,isopropanol, or propylene glycol, said fatty acid ester is a memberselected from the group consisting of polyethylene glycol laurate,3-acetylated sucrose denatured alcohol and diisopropyl adipate.
 25. Thepreparation according to claim 1 wherein the drug is a member selectedfrom the group consisting of a steroidal anti-inflammatory agent, anonsteroidal anti-inflammatory agent, an antiallergic agent, anantihistaminic agent, a central nervous system stimulant, a hormone, ananti-hypertensive agent, a cardiotonic agent, an antiarrhythmic agent, acoronary vasodilator, a local anesthetic, an analgesic agent, a skeletalmuscle relaxant, an antifungal agent, an antineoplastic agent, anantidysuric agent, an antiepileptic agent, an antiparkinson agent, asmoking-prohibition assistant agent, a vitamin, and prostaglandin. 26.The preparation according to claim 1 wherein the drug is a fat solublepowder in the amount of 0.001-20%, the preparation is a pack andcomprises, by weight, 0.001 to 5% of 3-l-menthoxy-propane-1,2-diol as asolubilizer and said fat soluble powder is a member selected from thegroup consisting of glycyrrhetinic acid, stearyl glycyrrhetinate,glycyrrhizinic acid, L-ascorbyl stearate, L-ascorbyl palmitate,calciferol, cholecalciferol, pionin and isopropylmethylphenyl thebalance being other ingredients as adjuvants for the preparation. 27.The preparation according to claim 26, wherein said balance comprisesglycerol, liquid paraffin, methyl paraben and purified water.